The present invention comprises a composition containing ephedrine base and an alkyl salicylate. The invention also relates to a method of delivering ephedrine base in vapor form from the composition of the invention. The invention further comprises articles of manufacture comprising the composition of the invention. The invention also further relates to the treatment of certain nasal and upper respiratory disorders by delivery of a therapeutically-effective amount of ephedrine base in a vapor form from the composition and articles of manufacture of the invention.
The common cold is usually accompanied by drainage from the nose (a "runny" nose), sneezing, cough, headache, and congestion in the nose, bronchus and lungs. One or more of these symptoms are generally relieved through systemic or topical application of an appropriate medication, such as cold tablets or capsules, cold rubs, nasal drops, nasal sprays, vapor inhalers, or others.
Ephedrine base (hereinafter also referred to simply as ephedrine) is well known to be useful in the treatment of various physiological disorders, including the symptoms of the common cold, and other disorders of the nasal mucosa and the respiratory tract. Other uses of ephedrine base include: the constriction of blood vessels; the bolstering of blood pressure of patients with spinal anesthesia; the treatment of shock; its use in the optometry field for its mydriatic effect; its use as a central nervous system (CNS) stimulant; the treatment of narcolepsy; the treatment of CNS poisoning by depressants, including barbiturates and morphine; and the treatment of myasthenia gravis.
In the treatment of these disorders, ephedrine has been used in a variety of forms and compositions. For example, sterile solutions of ephedrine have been used and administered subcutaneously, intravenously and muscularly. Solutions of ephedrine in a petroleum oil vehicle are applied topically from a level from about 1% to 3% by weight of the solution.
Ephedrine base has not been widely used in orally-administered forms such as tablets, capsules, elixirs and the like, to provide systemic delivery of the active, because it is rapidly metabolized in the body. Such an application usually utilizes a more stable active compound, particularly the salt forms of ephedrine (ephedrine sulfate or ephedrine hydrochloride), the isomer pseudoephedrine, and closely-related amine compounds such as desoxyephedrine, norephedrine, and epinephrine. As with all orally-administered actives, the onset of therapeutic activity is delayed due to the indirect delivery of the active via the digestive system through absorption into the bloodstream.
Ephedrine base is highly lipophilic and is absorbed readily through the skin and other mucosa. The transdermal adsorption of ephedrine base is several times faster than the corresponding ephedrine sulfate and hydrochloride forms. (See Transdermal Films of Ephedrine, Bhalla et al., Drug Development and Industrial Pharmacy, 14 (1), 119-131 (1988). Hence, ephedrine base can be a preferred compound for the treatment of disorders involving nasal mucosa and the respiratory tract if delivered directly to these areas.
There are minor problems associated with the use of ephedrine base in a product composition, including its instability in light (which can be overcome by appropriate packaging of the composition, for example, in a brown-glass bottle or sealed container), its tendency to form a more stable salt form in an aqueous solution without proper buffering, and its negligible volatility. In a petroleum oil or isotonic solution, ephedrine base exerts virtually no vapor pressure above a liquid containing as much as 10% by weight of ephedrine. Because of its poor volatility, ephedrine base has never been suggested or used in a composition or in a treatment where vapor phase delivery of the active is required. Rather, its use has been limited to direct application of the composition containing the ephedrine to a treatment site, such as the nasal cavity. Such forms are less effective and efficient since much of the active can be lost due to carrying away by natural body fluids of the mucosa, and since the liquid composition results in significant interference to effective absorption of the ephedrine by the mucosa or body tissue of the treatment site.
It would therefore be advantageous to deliver ephedrine base in the vapor phase in order to maximize absorption by the mucosa of the nasal and the upper respiratory cavity, to maximize the relative amount of surface area directly exposed to the active, and to reduce the loss of active via loss due to carrying away by natural body fluids.